The highlight of the conference this year was the presentation of “Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Guideline” on Sunday, March 8. This session, moderated by Dr. Laurence Kirschner (Ohio State Univ., Columbus, OH) was very well attended even on the last day of conference! The session included interactive questions that the audience could vote on and it was encouraging to see that the majority of the attendees chose the most appropriate answer to a question. The guidelines are produced by a task force of experts from across the world who look at the evidence in the medical literature for certain strategies of treatment. The panel was chaired by Dr. Lynnette Nieman (NIH, Bethesda, MD) and members of the task force were Dr. Beverly MK Biller (Mass. General Hospital, Boston, MA), Dr. James Findling (Medical College of Wisconsin, Milwaukee, WI), Dr. John Newell-Price (Univ. of Sheffield, Sheffield, United Kingdom) and Dr. Antoine Tabarin (Univ. of Bordeaux, Pressac, France). We cannot yet summarize the guidelines as they have not been published, but the CSRF did provide input during the review process. By far the most exciting development was that during the Q&A discussion, the CSRF was noted by panelist Dr. Beverly MK Biller as an example of a patient support organization that provides reliable patient information with Medical Advisory Board oversight. The CSRF has worked very hard for over 20 years to generate reliable information and it was very rewarding and encouraging to be recognized in this manner. Thank you!
During the scientific program, it was highly encouraging to see quality of life issues discussed. In a symposia titled “Novel Developments in Cushing’s.” Dr. Maya Beth Lodish (NIH, Bethesda, MD) presented on “Long Term Outcomes in Children” and noted the differences between Cushing’s in children and adolescents compared to adults. She also discussed the post-treatment challenges in children from both the physical and psychological/cognitive aspects (see article in this newsletter). Dr. Susan Webb (Hospital Sant Pau, Barcelona, Spain) then discussed “Long Term Outcomes in Adults” during which she highlighted that while physical, psychological, cognitive and quality of life issues improve after successful treatment, they may not completely resolve. She also discussed recent studies in the literature that demonstrate long term brain abnormalities following cure and impaired decision making. The symposia also included a talk on “Novel Mechanisms of Adrenal Cushing’s” by Dr. Herve Lefebvre (Univ. Hospital of Rouen, Rouen, France) which summarized some of the recent research in the area of molecular biology and genetics of adrenal Cushing’s. Another talk by Dr. Ashley Grossman (Churchill Hospital, Oxford, United Kingdom) titled “Therapeutic Strategies for Severe Cushing Syndrome” discussed the need to rapidly decrease cortisol levels in seriously ill patients. He discussed several medications with rapid onset and that initiation of anti-coagulants to prevent blood clots need to be considered in very ill patients.
In a symposium titled “Glucocorticoid Metabolism in Translation”, Dr. Jeremy Tomlinson, PhD (Univ. of Birmingham, Birmingham, United Kingdom” presented a talk titled, “Contribution of Liver vs Adipose Tissue Cortisol Metabolism to the Cushing’s Phenotype”. Dr. Tomlinson began by pointing out that glucocorticoids do different things in different tissues and went on to discuss studies with both liver and fat cells. Findings are that glucocorticoid metabolism in fat tissue is the most important contributor to weight gain and fatty liver associated with the Cushing’s phenotype. A second paper in this symposia , “Diurnal GC Delivery” (Merke D., NIH, Bethesda, MD) focused on the use of medications and pumps to provide cortisone replacement that mimics the natural secretion profile, which is presently viewed as the future of glucocorticoid replacement. Currently, these are primarily being studied in those with congenital adrenal hyperplasia.
Psychological and cognitive issues following treatment continue to be a subject of intense research. In an oral session, Glad, C. et al (Univ. of Gothenburg, Gothenburg, Sweden) presented preliminary results of a study that correlated fatigue, depression and anxiety with DNA changes in Cushing’s patients after long term remission. There were no differences between adrenal and pituitary Cushing’s patients, but patients differed from normal controls. In a poster, Andela, C. et al (Leiden Univ., Leiden, The Netherlands) presented a study on emotion processing in 21 Cushing’s patients in long term remission. In the study, an MRI was taken while showing patients human faces displaying different emotions. Results showed decreased activation of one brain region compared to normal controls. We are hopeful that eventually, increased understanding of these issues will lead to increased quality of life after treatment for Cushing’s.
In the area of testing for Cushing’s, Sharma T. and Nieman L. (NIH, Bethesda, MD) presented a poster on the subject of whether a normal 24 urinary cortisol rules out Cushing’s. Out of 72 patients, falsely normal results were obtained in 6 patients and another 13 patients had only slightly elevated results (< 2x the upper limit of normal). Thus, a single normal 24 urinary cortisol does not rule out Cushing’s and multiple collections and the use of other screening tests are highly advised in cases of suspected Cushing’s, particularly in mild cases. Amlashi F. et al (Mass. General Hospital) reported on the use of late night salivary cortisol (LNSC) and found that over a 10 year period, LNSC “may accurately establish remission of CD”. Another finding was when monitoring for recurrence of a pituitary tumor, LNSC may show an upwards trend earlier than 24hr urinary cortisol or overnight dexamethasone tests. In a poster studying pituitary MRI results in patients with ectopic Cushing’s, Sharma T. and Nieman L. (NIH, Bethesda, MD) found that a significant number of patients with ectopic Cushing’s had pituitary MRI’s that could be interpreted as showing a pituitary tumor. Unfortunately, a number of ectopic patients undergo unnecessary pituitary surgery prior to obtaining a correct diagnosis of ectopic Cushing’s.
In an oral poster preview, Steffensen, C. et al (Aarhus Univ. Hospital, Aarhus, Denmark) screened for Cushing’s in 505 consecutive patients newly diagnosed with Type II diabetes. They found that 4% of these patients had undiagnosed Cushing’s.
There were also a number of posters on medications for Cushing’s which included a new substance which shows promise for Cushing’s in dogs, reports on the use of the newer FDA approved medications, Korlym and Signifor and the currently open human clinical trials on Cor 003 and LCI 699. (See clinical trials in this newsletter.)
There were a number of interesting presentations in advances in imaging techniques which could be helpful in the years to come and many other items of future interest. As in all years, it is impossible to cover all of the work related to Cushing’s in a single article. The Cushing’s community should be thankful that we have so many excellent researchers working in this area.
You can read the abstracts yourself.
Authors: Karen Campbell, reviewed by Dr. James Findling, Spring, 2015
Editor’s note: Karen Campbell is Director, CSRF. Dr. James Findling is Professor of Medicine, Endocrinology and Metabolism at the Medical College of Wisconsin, Milwaukee, WI and on the CSRF Board of Directors.